This invention relates to semi-synthetic cephalosporin antibiotic compounds. In particular, it relates to cephalosporin compounds represented by the following formula ##STR2## wherein R is a 5-membered hetrocyclic ring containing oxygen and nitrogen atoms, R' is hydrogen, C.sub.1 -C.sub.4 alkyl, an N-substituted carbamoyl group or a carboxy-substituted alkyl or cycloalkyl group, and .sup..sym. R.sub.1 is pyridinium, quinolinium, or isoquinolinium, each bearing an oximino substituent group.
The compounds of the invention are cephalosporin betaines characterized by the inner salt formed with the C.sub.4 carboxylate anion and the cation of the quaternary heterocyclic group .sup..sym. R.sub.1.
Cephalosporin antibiotics substituted in the 3'-position by a quaternary ammonium group have been known for some time. One of the first derivations of cephalosporin C which was discovered was cephalosporin C.sub.A (pyridine), Hale, Newton, and Abraham, Biochem. J., 79, 403 (1961). Cephaloridine, the well-known clinical antibiotic is the 3'-pyridinium, 7-(.alpha.-thienylactamido)-3-(pyridinium-1-ylmethyl)-3-cephem-4-carboxyla te.
Recently, Heymes et al., U.S. Pat. No. 4,152,432, described semi-synthetic cephalosporin compounds having a 7-[2-(2-aminothiazol-4-yl)-2-alkoxyiminoacetamido] side chain group in the 7-position of the bicyclic cephem ring system, while the acetoxymethyl group is the 3-position substituent. Others have prepared 3'-pyridinium-substituted derivatives of this type of oximino-substituted cephalosporin. For example, Ochiai et al., U.S. Pat. No. 4,278,671 describe 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(pyridinium -1-ylmethyl)-3-cephem-4-carboxylate, and O'Callaghan et al., U.S. Pat. No. 4,258,041, describe ceftazidime, 7-[2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-yl)oxyiminoacetamido]-3-(pyr idinium-1-ylmethyl)-3-cephem-4-carboxylate.
Continuing research with the cephalosporin antibiotics has as one of its goals the development of antibiotics to overcome the deficiencies in current antibiotic therapy. For example, there exists the need for cephalosporin antibiotics with greater potency against the gram-negative bacteria such as pseudomonas, and with inhibitory activity against microorganisms which are resistant to the presently known antibiotics.
The cephalosporin compounds of this invention are structurally novel compounds which possess high activity against the gram-negative bacteria with retention of high activity against the gram-positive microorganisms.